Gardasil VaccinePhase 1NCT01092195
Gardasil Vaccination in Post Stem Cell Transplant Patients
A Phase 1 study testing Gardasil in people with Gardasil Vaccine and Stem Cell Transplant, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Gardasil , a recently approved vaccine for the sexually transmitted human papillomavirus (HPV), provides immunity to four types of HPV that are associated with genital warts and cervical, vaginal, and vulvar precancer and cancer. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Gardasil Vaccine, Stem Cell Transplant, Immunogenicity
- What is being tested?
- Gardasil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2010to 19 Jul 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female stem cell transplant recipient at least 90 days post stem cell transplant
- OR
- Female stem cell transplant recipient at least 90 days post HSCT and on immunosuppression
- OR
- The matched female stem cell transplant donor for an included stem cell transplant recipient
- OR
- Healthy female subject
- Age greater than or equal to 18 years and less than or equal to 50 years
Who cannot join
- Vaccine Recipient:
- Obvious HPV condyloma or obvious severe dysplasia (greater than or equal to CIN II) warranting treatment
- History of severe adverse reaction to any components (yeast, eggs, monosodium glutamate or neomycin) of the quadrivalent HPV vaccine.
- Untreated or persistent life-threatening infections not controlled by current treatment
- Uncontrolled chronic GVHD i.e. highly active eGVHD requiring immediate intervention
- Pregnant or breast feeding or unwilling to be abstinent or practice effective contraception during the study period (note: patients who have been rendered infertile with total body irradiation are eligible)
Show all 11Show fewer
- Enrollment in another vaccine clinical trial during the study period
- Enrollment of healthy volunteer in a drug clinical trial during the study period
- Inability to comprehend the investigational nature of the study and provide informed consent<TAB>
- Prior Gardasil or other HPV vaccination
- Persistent or recurrent malignancy
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of Safety and Immunogenicity of Gardasil Vaccination Post Stem Cell Transplantation in Patients With and Without Immunosuppression
Background:
- Gardasil , a recently approved vaccine for the sexually transmitted human papillomavirus (HPV), provides immunity to four types of HPV that are associated with genital warts and cervical, vaginal, and vulvar precancer and cancer. The vaccine has been shown to be highly effective in preventing infection with these HPV types and was approved for use by the Food and Drug Administration.
- More research is needed about the vaccine s ability to induce immunity in individuals with suppressed immune systems, such as those who have had other kinds of cancer treatment such as stem cell transplant. Genital warts, precancer, and cancer have been reported as a late complication after stem cell transplant. Researchers are interested in determining whether the HPV vaccine is safe to give and able to induce immunity in female stem cell transplant recipients, their female donors, and healthy female volunteers.
Read more
Objectives:
- To assess the safety and immune response of the HPV vaccine in female recipients of stem cell transplants who are either off or on stable doses of immunosuppression.
Eligibility:
- Females between 18 and 50 years of age who have had allogenic stem cell transplants.
- Healthy female volunteers, including stem cell donors, are also eligible for this study.
Design:
- Participants will be screened with a physical examination, blood and urine tests, and saliva samples, and will be asked to complete a sexual quality of life questionnaire.
- Sexually active participants will also have a routine gynecologic evaluation.
- Participants will receive three HPV vaccinations according to the standard vaccination schedule (with the second and third following 2 and 6 months after the first). Participants will record their daily temperature and any reactions to the vaccine on a vaccine report card for 1 week after each vaccination.
- Participants will have clinic visits for further testing 2, 6, 7, and 12 months after receiving the first HPV vaccine.
Read the detailed description
HPV associated genital dysplasia is a complication following hematopoietic allogeneic stem cell transplantation (HSCT). In a recent study from this institution, one third of female transplant recipients had HPV related genital tract dysplasia. The quadrivalent human papillomavirus virus (HPV) (types 6, 11, 16, 18) vaccine (Gardasil ) is now approved for use in females aged 9-26 for the prevention of cervical cancer and, more recently, vulvar and vaginal cancer. In this study, Gardasil will be used in females age 18 years to 50 at least 90 days post stem cell transplant in two study cohorts to determine its safety and immunogenicity in this population, as a first step to reduce post-transplant HPV-related co-morbidity, genital dysplasia and malignancy. The two study cohorts will both be post transplant; one off of immunosuppression (n=24), and one on immunosuppression (n=24). Gardasil will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. The primary objectives of this study are to determine the safety and immunogenicity of Gardasil in female allogeneic HSCT recipients. A cohort of healthy subjects will also be vaccinated (n=24) and will serve as a control. Immunogenicity studies characterizing the CD4 and CD8 T- cell response, change in antibody titer and cytokine response from baseline to months seven and twelve will be compared in the three cohorts. Additionally, genital exams will be performed to monitor for HPV. Secondary endpoints will characterize sexual function post-transplant and vulvar/vaginal graft-versus-host disease (GVHD). When available, healthy female stem cell donors corresponding to enrolled vaccine recipients will be enrolled (n=10) as part of the healthy cohort and vaccinated to determine whether there are differences in HPV vaccine immunogenicity in a subset of donors and their respective allogeneic, HSCT female recipients.
As stem cell transplant becomes more applicable to the general population with newer transplant techniques allowing for a larger donor pool and as survival improves, problems associated with long term survivorship such as genital dysplasia, will become more prevalent. Vaccine therapy to prevent or eradicate this disease is needed.
- Conditions
- Gardasil Vaccine, Stem Cell Transplant, Immunogenicity
- Being tested
- Gardasil
- Keywords
- Women's Health, Genital Precancer, Stem Cell Donor, Cervical Cytology, Healthy Volunteers, Stem Cell Transplant, Healthy Volunteer, HV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GardasilBiological
3 separate 0.5 ml intramuscular
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Active comparator | Female subjects post stem cell transplant on no systemic immunosuppression. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. Receives: Biological: Gardasil |
| Cohort 2 | Active comparator | Female subjects post stem cell transplant with chronic GVHD requiring systemic immunosuppression. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. Receives: Biological: Gardasil |
| Cohort 3 | Active comparator | Healthy normal female volunteers. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. Receives: Biological: Gardasil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Who Developed Antibody Response to the Vaccine.
The percentage of subjects who developed antibody response to the quadrivalent HPV (qHPV) vaccine (HPV - 6/ - 11/ - 16/ - 18). Anti-HPV-6/11/16/18-specific antibody responses using L1 Virus Like Particle (VLP) ELISA were measured in serum.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2010 (estimated)
- Study start2 Jun 2010
- Primary completion19 Jul 2016
- Study completion19 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Gardasil VaccineStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard W Childs, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01092195
- Sponsor's protocol ID
- 100083
- Other IDs
- 10-H-0083
- Status last verified
- Jul 2018
- First submitted
- 23 Mar 2010
- Last updated
- 6 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6;348(6):518-27. doi: 10.1056/NEJMoa021641.
PubMed 12571259Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev. 1988;10:122-63. doi: 10.1093/oxfordjournals.epirev.a036020.
PubMed 2852116Koshiol JE, Laurent SA, Pimenta JM. Rate and predictors of new genital warts claims and genital warts-related healthcare utilization among privately insured patients in the United States. Sex Transm Dis. 2004 Dec;31(12):748-52. doi: 10.1097/01.olq.0000145851.76025.ad.
PubMed 15608590Stratton P, Battiwalla M, Tian X, Abdelazim S, Baird K, Barrett AJ, Cantilena CR, Childs RW, DeJesus J, Fitzhugh C, Fowler D, Gea-Banacloche J, Gress RE, Hickstein D, Hsieh M, Ito S, Kemp TJ, Khachikyan I, Merideth MA, Pavletic SZ, Quint W, Schiffman M, Scrivani C, Shanis D, Shenoy AG, Struijk L, Tisdale JF, Wagner S, Williams KM, Yu Q, Wood LV, Pinto LA. Immune Response Following Quadrivalent Human Papillomavirus Vaccination in Women After Hematopoietic Allogeneic Stem Cell Transplant: A Nonrandomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):696-705. doi: 10.1001/jamaoncol.2019.6722.
PubMed 32105293
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Safety and Immunogenicity of Gardasil Vaccination Post Stem Cell Transplantation in Patients With and Without Immunosuppression
- ClinicalTrials.gov ID
- NCT01092195
- Acronym / sponsor ID
- 100083
- Conditions
- Gardasil Vaccine, Stem Cell Transplant, Immunogenicity
- Keywords
- Women's Health, Genital Precancer, Stem Cell Donor, Cervical Cytology, Healthy Volunteers, Stem Cell Transplant, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 2 Jun 2010 (actual)
- Primary completion
- 19 Jul 2016 (actual)
- Study completion
- 19 Jul 2016 (actual)
- First posted
- 24 Mar 2010 (estimated)
- Results
- Posted 1 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Gardasil , a recently approved vaccine for the sexually transmitted human papillomavirus (HPV), provides immunity to four types of HPV that are associated with genital warts and cervical, vaginal, and vulvar precancer and cancer. The vaccine has been shown to be highly effective in preventing infection with these HPV types and was approved for use by the Food and Drug Administration.
- More research is needed about the vaccine s ability to induce immunity in individuals with suppressed immune systems, such as those who have had other kinds of cancer treatment such as stem cell transplant. Genital warts, precancer, and cancer have been reported as a late complication after stem cell transplant. Researchers are interested in determining whether the HPV vaccine is safe to give and able to induce immunity in female stem cell transplant recipients, their female donors, and healthy female volunteers.
Objectives:
- To assess the safety and immune response of the HPV vaccine in female recipients of stem cell transplants who are either off or on stable doses of immunosuppression.
Eligibility:
- Females between 18 and 50 years of age who have had allogenic stem cell transplants.
- Healthy female volunteers, including stem cell donors, are also eligible for this study.
Design:
- Participants will be screened with a physical examination, blood and urine tests, and saliva samples, and will be asked to complete a sexual quality of life questionnaire.
- Sexually active participants will also have a routine gynecologic evaluation.
- Participants will receive three HPV vaccinations according to the standard vaccination schedule (with the second and third following 2 and 6 months after the first). Participants will record their daily temperature and any reactions to the vaccine on a vaccine report card for 1 week after each vaccination.
- Participants will have clinic visits for further testing 2, 6, 7, and 12 months after receiving the first HPV vaccine.
Detailed description
HPV associated genital dysplasia is a complication following hematopoietic allogeneic stem cell transplantation (HSCT). In a recent study from this institution, one third of female transplant recipients had HPV related genital tract dysplasia. The quadrivalent human papillomavirus virus (HPV) (types 6, 11, 16, 18) vaccine (Gardasil ) is now approved for use in females aged 9-26 for the prevention of cervical cancer and, more recently, vulvar and vaginal cancer. In this study, Gardasil will be used in females age 18 years to 50 at least 90 days post stem cell transplant in two study cohorts to determine its safety and immunogenicity in this population, as a first step to reduce post-transplant HPV-related co-morbidity, genital dysplasia and malignancy. The two study cohorts will both be post transplant; one off of immunosuppression (n=24), and one on immunosuppression (n=24). Gardasil will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. The primary objectives of this study are to determine the safety and immunogenicity of Gardasil in female allogeneic HSCT recipients. A cohort of healthy subjects will also be vaccinated (n=24) and will serve as a control. Immunogenicity studies characterizing the CD4 and CD8 T- cell response, change in antibody titer and cytokine response from baseline to months seven and twelve will be compared in the three cohorts. Additionally, genital exams will be performed to monitor for HPV. Secondary endpoints will characterize sexual function post-transplant and vulvar/vaginal graft-versus-host disease (GVHD). When available, healthy female stem cell donors corresponding to enrolled vaccine recipients will be enrolled (n=10) as part of the healthy cohort and vaccinated to determine whether there are differences in HPV vaccine immunogenicity in a subset of donors and their respective allogeneic, HSCT female recipients.
As stem cell transplant becomes more applicable to the general population with newer transplant techniques allowing for a larger donor pool and as survival improves, problems associated with long term survivorship such as genital dysplasia, will become more prevalent. Vaccine therapy to prevent or eradicate this disease is needed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Active comparator | Biological: GardasilFemale subjects post stem cell transplant on no systemic immunosuppression. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. |
| Cohort 2 | Active comparator | Biological: GardasilFemale subjects post stem cell transplant with chronic GVHD requiring systemic immunosuppression. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. |
| Cohort 3 | Active comparator | Biological: GardasilHealthy normal female volunteers. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Female stem cell transplant recipient at least 90 days post stem cell transplant
- OR
- Female stem cell transplant recipient at least 90 days post HSCT and on immunosuppression
- OR
- The matched female stem cell transplant donor for an included stem cell transplant recipient
Key exclusion criteria (11 listed)
- Obvious HPV condyloma or obvious severe dysplasia (greater than or equal to CIN II) warranting treatment
- History of severe adverse reaction to any components (yeast, eggs, monosodium glutamate or neomycin) of the quadrivalent HPV vaccine.
- Untreated or persistent life-threatening infections not controlled by current treatment
- Uncontrolled chronic GVHD i.e. highly active eGVHD requiring immediate intervention
- Pregnant or breast feeding or unwilling to be abstinent or practice effective contraception during the study period (note: patients who have been rendered infertile with total body irradiation are eligible)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gardasil3 separate 0.5 ml intramuscular | Biological | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Percentage of Subjects Who Developed Antibody Response to the Vaccine.
Time frame: 12 months
The percentage of subjects who developed antibody response to the quadrivalent HPV (qHPV) vaccine (HPV - 6/ - 11/ - 16/ - 18). Anti-HPV-6/11/16/18-specific antibody responses using L1 Virus Like Particle (VLP) ELISA were measured in serum.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12571259Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6;348(6):518-27. doi: 10.1056/NEJMoa021641.
- Background: PubMed 2852116Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev. 1988;10:122-63. doi: 10.1093/oxfordjournals.epirev.a036020.
- Background: PubMed 15608590Koshiol JE, Laurent SA, Pimenta JM. Rate and predictors of new genital warts claims and genital warts-related healthcare utilization among privately insured patients in the United States. Sex Transm Dis. 2004 Dec;31(12):748-52. doi: 10.1097/01.olq.0000145851.76025.ad.
- Derived from this study: PubMed 32105293Stratton P, Battiwalla M, Tian X, Abdelazim S, Baird K, Barrett AJ, Cantilena CR, Childs RW, DeJesus J, Fitzhugh C, Fowler D, Gea-Banacloche J, Gress RE, Hickstein D, Hsieh M, Ito S, Kemp TJ, Khachikyan I, Merideth MA, Pavletic SZ, Quint W, Schiffman M, Scrivani C, Shanis D, Shenoy AG, Struijk L, Tisdale JF, Wagner S, Williams KM, Yu Q, Wood LV, Pinto LA. Immune Response Following Quadrivalent Human Papillomavirus Vaccination in Women After Hematopoietic Allogeneic Stem Cell Transplant: A Nonrandomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):696-705. doi: 10.1001/jamaoncol.2019.6722.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard W Childs, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gardasil in people with Gardasil Vaccine and Stem Cell Transplant, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects Who Developed Antibody Response to the Vaccine. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01092195, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.